SUMMARY During the Cenozoic, the Earth experienced multiple first-order geological events that are likely mantle flow related. These include the termination of large-scale marine inundation in North America in the Palaeocene, the late Tertiary rise of Africa relative to other continents and the long-wavelength tilting of Australia since the late Cretaceous, which occurred when the continent approached the southeast Asia subduction systems on its northward passage from Antartica. Here we explore a suite of eight high-resolution, compressible, global mantle flow retrodictions going back to 50 Ma, using an adoint method with $\approx$670 million finite elements. These retrodictions show for the first time that these events emerge jointly as part of global Cenozoic mantle flow histories. Our retrodictions involve the dynamic effects from an upper mantle low-viscosity zone, assimilate a past plate-motion model for the tangential surface velocity field, probe the influence of two different present-day mantle state estimates derived from seismic tomography, and acknowledge the rheological uncertainties of dynamic Earth models by taking in four different realizations for the radial mantle viscosity profile, two of which were published previously. We find the retrodicted mantle flow histories are sensitive to the present-day mantle state estimate and the rheological properties of the Earth model, meaning that this input information is testable with inferences gleaned from the geological record. For a deep mantle viscosity of $1.7\times 10^{22}$ Pa s and a purely thermal interpretation of seismic structure, lower mantle flow velocities exceed 7 cm yr–1 in some regions, meaning they are difficult to reconcile with the existence of a hotspot reference frame. Conversely, a deep mantle viscosity of $10^{23}$ Pa s yields modest flow velocities (< 3 cm yr–1 ) and stability of deep mantle heterogeneity for much of the retrodiction time, albeit at the expense that African uplift is delayed into the latest Neogene. Retrodictions allow one to track material back in time from any given sampling location, making them potentially useful, for example, to geochemical studies. Our results call for improved estimates on non-isostatic vertical motion of the Earth’s surface—provided, for instance, by basin analysis, seismic stratigraphy, landform studies, thermochronological data or the sedimentation record—to constrain the recent mantle flow history and suggest that mantle flow retrodictions may yield synergies across different Earth science disciplines.